Santeliz Sonia, Caicedo Peter, Giraldo Elidiosmar, Alvarez Carmen, Yustiz María-Daniela, Rodríguez-Bonfante Claudina, Bonfante-Rodríguez Romina, Bonfante-Cabarcas Rafael
Decanato de Ciencias Veterinarias, Unidad de Biomedicina, Departamento de Medicina y Cirugía, Barquisimeto, Estado Lara, Venezuela.
Decanato de Ciencias de la Salud, Unidad de Bioquímica, Barquisimeto, Estado Lara, Venezuela.
Mem Inst Oswaldo Cruz. 2017 Sep;112(9):596-608. doi: 10.1590/0074-02760160499.
As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy.
To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease.
NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods.
In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved.
DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.
由于慢性恰加斯病尚无确切的治疗方法，开发替代治疗方案是当务之急。双嘧达莫（DPY）是一种可用于对抗恰加斯心肌病相关病理生理现象的替代药物。
评估DPY与硝呋替莫（Nfx）联合应用于无鞭毛体体外培养以及急性恰加斯病小鼠的治疗效果。
将成年雄性NMRI小鼠分为九组：三组健康组和六组感染克氏锥虫组。小鼠单独或联合接受赋形剂、Nfx或DPY。所测定的剂量为Nfx 10和40 mg/kg以及DPY 30 mg/kg。通过临床、心电图、寄生虫学、生化和组织病理学方法评估治疗效果。
在体外，DPY和Nfx具有杀锥虫作用，IC50值分别为372±52和21.53±2.13 μM；DPY增强了Nfx的作用。在体内，Nfx（40 mg/kg）无论是否联合DPY均具有治疗效果，这体现在84% - 92%的生存率以及寄生虫血症和心脏组织无鞭毛体的消除。Nfx（10 mg/kg）具有亚治疗效果，无生存率，心脏组织中无鞭毛体持续存在、有炎症和纤维化；添加DPY可使生存率提高至85%，且所有测试参数均有显著改善。
DPY在体外具有杀锥虫作用，并在体内小鼠模型中增强了Nfx的治疗效果。
